CN103193666B - The preparation method of 2-amino-3-chloro benzoic ether - Google Patents
The preparation method of 2-amino-3-chloro benzoic ether Download PDFInfo
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- CN103193666B CN103193666B CN201310122262.0A CN201310122262A CN103193666B CN 103193666 B CN103193666 B CN 103193666B CN 201310122262 A CN201310122262 A CN 201310122262A CN 103193666 B CN103193666 B CN 103193666B
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Abstract
The invention discloses a kind of preparation method of 2-amino-3-chloro benzoic ether, the method detailed process is as follows: 1. under room temperature, in the 2-amino-3-chloro-benzoic acid being dissolved in organic solvent, add mineral alkali; 2., after adding, be cooled to 5 DEG C ~ 10 DEG C and stir 0.1h ~ 1h, slowly dripping methylating reagent; 3. after dripping off, at room temperature stirring reaction 4h ~ 8h; 4. filter, filter cake, after washing, drying, obtains 2-amino-3-chloro benzoic ether.The present invention adopts methylating reagent and 2-amino-3-chloro-benzoic acid to carry out esterification, and reaction process is simple, and processing ease, security is good, and cost is low, and the product purity particularly obtained is higher, and yield is also higher, is very suitable for suitability for industrialized production.In addition, after reaction of the present invention terminates, adopt enough water to be separated out from reacted material by product, so not only further increase yield, and separate out after product color better.
Description
Technical field
The present invention relates to a kind of preparation method of herbicide intermediate, specifically relate to a kind of preparation method of 2-amino-3-chloro benzoic ether.
Background technology
2-amino-3-chloro benzoic ether is an important pharmaceutical-chemical intermediate, and it is the key intermediate of synthesis triazolopyrimidine sulfonamides herbicide cloransulammethyl, and has application in the synthesis of many agricultural chemicals.
Preparation both at home and abroad about 2-amino-3-chloro benzoic ether mainly contains following several method:
American documentation literature US4306074A discloses a kind of preparation method of 2-amino-3-chloro benzoic ether, it obtains 3-chloroisatoic anhydride and 6-chloroisatoic anhydride by 3-chloro-phthalic anhydride through amination and Hofmann degradation, then carries out esterification and obtain 2-amino-3-chloro benzoic ether and 2-amino-6-chloro benzoic ether.The deficiency of the method is: (1) reaction process is complicated; (2) can obtain more by product 2-amino-6-chloro benzoic ether, yield is lower, and purity is not high yet.
American documentation literature US5118832A discloses a kind of preparation method of 2-amino-3-chloro benzoic ether, and it is by 2-Methyl anthranilate and chloro-5, the 5-T10s of DDH(1,3-bis-) be obtained by reacting in the organic solvents such as tetracol phenixin.The deficiency of the method is: (1) can obtain more by product 2-amino-5-chloro benzoic ether and amino-3, the 5-methyl p-dichlorobenzenes of part by product 2-, and yield is lower, and purity is not high yet.(2) raw material DDH is expensive and be difficult to obtain, and is unsuitable for suitability for industrialized production.
American documentation literature US5557005A discloses a kind of preparation method of 2-amino-3-chloro benzoic ether, it first obtains 3-chloroisatoic anhydride with phosgene reaction by 2-amino-3-chloro-benzoic acid, and then carry out esterification with methyl alcohol and obtain 2-amino-3-chloro benzoic ether.The deficiency of the method is: (1) reaction process is complicated; (2) reaction process needs the phosgene passing into severe toxicity, is absolutely unsafe.
Volume the 2nd phase in " University Of Xiangtan's natural science journal " June the 29th in 2007 57th ~ 59 pages discloses a kind of 2, the new synthetic method of 3-dichlorobenzoic acid, it is disclosed that a kind of preparation method of 2-amino-3-chloro benzoic ether: in 250mL there-necked flask, add 29.1g(0.17mol) 2-amino-3-chloro-benzoic acid and 100mL anhydrous methanol, pass into dry HCl gas 15L(and be about 0.68mol), reflux 6h, solution is poured in 250mL water after cool to room temperature, pH=8 ~ 9 are adjusted to saturated sodium bicarbonate solution, separate out white solid 30.2g, yield is 96%.The deficiency of the method is: need to pass into HCl gas in (1) reaction process, not only wayward, and security is poor; (2) product purity is lower, about 90%, is not suitable for suitability for industrialized production; (3) applicant adopts the method for the document to carry out many experiments, and yield is the highest also only has 92.7%, do not reach 96% alleged by it, and product color is not good, slightly yellowing at all.
Summary of the invention
The object of the invention is to solve the problem, provide that a kind of reaction process is simple and easy to control, product purity is higher and the preparation method of the 2-amino-3-chloro benzoic ether that yield is also higher.
The technical scheme realizing the object of the invention is: a kind of preparation method of 2-amino-3-chloro benzoic ether, and it is obtained by reacting under the existence of mineral alkali and organic solvent by 2-amino-3-chloro-benzoic acid and methylating reagent.
Detailed process is as follows: 1. under room temperature (15 DEG C ~ 25 DEG C, lower with), in the 2-amino-3-chloro-benzoic acid being dissolved in organic solvent, add mineral alkali; 2., after adding, be cooled to 5 DEG C ~ 10 DEG C and stir 0.1h ~ 1h, slowly dripping methylating reagent; 3. after dripping off, at room temperature stirring reaction 4h ~ 8h; 4. filter, filter cake, after washing, drying, obtains 2-amino-3-chloro benzoic ether.
Reaction times after above-mentioned dropping methylating reagent can not be long, otherwise can produce a large amount of impurity, has a strong impact on product purity.
Above-mentioned steps 4. in also comprise: reacted material is mixed (be added to the water by reacted material or add water in reacted material) with water and stirs 0.5h ~ 1.5h before filtering; The weight ratio of described water and described 2-amino-3-chloro-benzoic acid is 10: 1 ~ 15: 1.Reacted material and enough water are mixed with and are beneficial to product and separate out completely, can improve yield so on the one hand, the product color after separating out on the other hand is also better.
Described methylating reagent is methyl-sulfate and/or methylcarbonate, preferably sulfuric acid dimethyl ester; Described 2-amino-3-chloro-benzoic acid and the mol ratio of described methylating reagent are 1: 1 ~ 1: 2.
Described mineral alkali is the one in salt of wormwood, sodium carbonate, sodium bicarbonate, saleratus, sodium hydroxide and potassium hydroxide, preferred salt of wormwood; Described 2-amino-3-chloro-benzoic acid and the mol ratio of described mineral alkali are 1: 0.5 ~ 1: 1.
Described organic solvent is the one in DMF (DMF), N,N-dimethylacetamide (DMAC) and N-Methyl pyrrolidone (NMP); Described 2-amino-3-chloro-benzoic acid and the weight ratio of described organic solvent are 1: 3 ~ 1: 7.
Reaction equation of the present invention is as follows:
The positively effect that the present invention has: (1) the present invention adopts methylating reagent and 2-amino-3-chloro-benzoic acid to carry out esterification, reaction process is simple, processing ease, security is good, and cost is low, and the product purity particularly obtained is higher, yield is also higher, is very suitable for suitability for industrialized production.(2), after reaction of the present invention terminates, adopt enough water to be separated out from reacted material by product, so not only further increase yield, and separate out after product color better.
Embodiment
(embodiment 1)
1. under room temperature, in the reaction flask of 500mL, add the DMF of 150g, then add 2-amino-3-chloro-benzoic acid (0.175mol) of 30g, then add the salt of wormwood (0.125mol) of 17.3g again.
2. after adding, be cooled to 10 DEG C and stir 0.5h, slowly dripping the methyl-sulfate (0.178mol) of 22.4g.
3., after dripping off, room temperature is risen to and stirring reaction 6h.
4. pour in 400mL water by reacted material, separate out white solid, after stirring 1h, filter, filter cake is through the 2-amino-3-chloro benzoic ether washed, drying obtains 31.8g, and yield is 95.0%, and purity is 97%(HPLC).
(embodiment 2 ~ embodiment 4)
The preparation method of each embodiment is substantially the same manner as Example 1, and difference is in table 1.
Table 1
As can be seen from Table 1, adopt salt of wormwood to be slightly better than sodium carbonate as the effect of mineral alkali, and adopt methyl-sulfate to be also slightly better than methylcarbonate as the effect of methylating reagent.
(embodiment 5)
1. under room temperature, in the reaction flask of 500mL, add the DMF of 150g, then add 2-amino-3-chloro-benzoic acid (0.175mol) of 30g, then add the salt of wormwood (0.125mol) of 17.3g again.
2. after adding, be cooled to 10 DEG C and stir 0.5h, slowly dripping the methyl-sulfate (0.178mol) of 22.4g.
3., after dripping off, room temperature is risen to and stirring reaction 6h.
4. by reacted material direct filtration, filter cake is through the 2-amino-3-chloro benzoic ether washed, drying obtains 30.8g, and yield is 91.1%, and purity is 96%(HPLC).
From embodiment 1 and embodiment 5, step 4. in, reacted material is poured into water and is conducive to product and separates out completely, thus yield is higher.
(comparative example)
In 250mL there-necked flask, add 30g(0.175mol) 2-amino-3-chloro-benzoic acid and 100mL anhydrous methanol, pass into the HCl gas of 15L drying, reflux 6h, pours into solution in 250mL water after cool to room temperature, is adjusted to pH=9 with saturated sodium bicarbonate solution, then filter, washing filter cake is also dry, and obtain the 2-amino-3-chloro benzoic ether of 32.7g, yield is 92.7%, purity is 92%(HPLC), product is yellowing slightly.
Claims (4)
1. a preparation method for 2-amino-3-chloro benzoic ether, is characterized in that having following steps:
1., under room temperature, in the 2-amino-3-chloro-benzoic acid being dissolved in organic solvent, mineral alkali is added;
2., after adding, be cooled to 5 DEG C ~ 10 DEG C, and stir 0.1h ~ 1h, slowly drip methylating reagent;
3. after dripping off, at room temperature stirring reaction 4h ~ 8h;
4. reacted material is mixed with water, and stir 0.5h ~ 1.5h; The weight ratio of described water and described 2-amino-3-chloro-benzoic acid is 10: 1 ~ 15: 1;
Filter, filter cake, after washing, drying, obtains 2-amino-3-chloro benzoic ether.
2. the preparation method of 2-amino-3-chloro benzoic ether according to claim 1, is characterized in that: described methylating reagent is methyl-sulfate and/or methylcarbonate; Described 2-amino-3-chloro-benzoic acid and the mol ratio of described methylating reagent are 1: 1 ~ 1: 2.
3. the preparation method of 2-amino-3-chloro benzoic ether according to claim 1, is characterized in that: described mineral alkali is the one in salt of wormwood, sodium carbonate, sodium bicarbonate, saleratus, sodium hydroxide and potassium hydroxide; Described 2-amino-3-chloro-benzoic acid and the mol ratio of described mineral alkali are 1: 0.5 ~ 1: 1.
4. the preparation method of 2-amino-3-chloro benzoic ether according to claim 1, is characterized in that: described organic solvent is the one in DMF, N,N-dimethylacetamide and N-Methyl pyrrolidone; Described 2-amino-3-chloro-benzoic acid and the weight ratio of described organic solvent are 1: 3 ~ 1: 7.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107018987A (en) * | 2017-05-09 | 2017-08-08 | 王亮 | Herbicide |
| CN107266324A (en) * | 2017-07-17 | 2017-10-20 | 常州大学 | A kind of synthetic method of the chloro benzoic ether of 2 amino 3 |
| CN108047069A (en) * | 2017-12-29 | 2018-05-18 | 南通泰禾化工股份有限公司 | A kind of preparation method of 2- amino -3- chloro benzoic ethers |
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| US4306074A (en) * | 1977-06-20 | 1981-12-15 | Basf Aktiengesellschaft | Preparation of a mixture of an alkyl 3-chloroanthranilate and an alkyl 6-chloroanthranilate |
| US5118832A (en) * | 1991-06-14 | 1992-06-02 | Dowelanco | Process for the preparation of alkyl 3-chloroanthranilates |
| CN1112105A (en) * | 1993-09-18 | 1995-11-22 | 赫彻斯特股份公司 | Method for preparation 3-hydroxy-2,4,5-trifluorbenzoealkyl formate and/or 3-alkoxy-2,4,5-trifluorbenzoealkyformate |
| US5557005A (en) * | 1993-04-22 | 1996-09-17 | Hoechst Aktiengesellschaft | Process for preparing 3-chloroanthranilic alkyl esters of high purity from 3-chloroanthranilic acid |
| CN102351707A (en) * | 2011-11-18 | 2012-02-15 | 苏州诚和医药化学有限公司 | Method for preparing methyl o-anisate |
| TW201311616A (en) * | 2011-07-07 | 2013-03-16 | Ihara Chemical Ind Co | Nitrobenzene compound manufacturing method |
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- 2013-04-09 CN CN201310122262.0A patent/CN103193666B/en active Active
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| US4306074A (en) * | 1977-06-20 | 1981-12-15 | Basf Aktiengesellschaft | Preparation of a mixture of an alkyl 3-chloroanthranilate and an alkyl 6-chloroanthranilate |
| US5118832A (en) * | 1991-06-14 | 1992-06-02 | Dowelanco | Process for the preparation of alkyl 3-chloroanthranilates |
| US5557005A (en) * | 1993-04-22 | 1996-09-17 | Hoechst Aktiengesellschaft | Process for preparing 3-chloroanthranilic alkyl esters of high purity from 3-chloroanthranilic acid |
| CN1112105A (en) * | 1993-09-18 | 1995-11-22 | 赫彻斯特股份公司 | Method for preparation 3-hydroxy-2,4,5-trifluorbenzoealkyl formate and/or 3-alkoxy-2,4,5-trifluorbenzoealkyformate |
| TW201311616A (en) * | 2011-07-07 | 2013-03-16 | Ihara Chemical Ind Co | Nitrobenzene compound manufacturing method |
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| 2,3-二氯苯甲酸的合成新方法;林原斌等;《湘潭大学自然科学学报》;20070615;第29卷(第02期);57-59、110 * |
| 2,3-二氯苯甲酸的合成新方法;林原斌等;《湘潭大学自然科学学报》;20070615;第29卷(第02期);57-60 * |
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